Johnson Julia A, Albu Jeanine B, Engelson Ellen S, Fried Susan K, Inada Yoritaro, Ionescu Gabriel, Kotler Donald P
Obesity Research Center, St. Luke's Roosevelt Hospital Center, College of Physicians and Surgeons, Columbia University, New York, NY 10025, USA.
Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E261-71. doi: 10.1152/ajpendo.00056.2003. Epub 2003 Oct 7.
The lipodystrophy syndrome (adipose tissue redistribution and metabolic abnormalities) observed with highly active antiretroviral therapy (HAART) during human immunodeficiency virus (HIV) infection may be related to increased proinflammatory cytokine activity. We measured acute cytokine (TNF-alpha, IL-6, leptin), glycerol, and lactate secretion from abdominal subcutaneous adipose tissue (SAT), and systemic cytokine levels, in HIV-infected subjects with and without lipodystrophy (HIVL+ and HIVL-, respectively) and healthy non-HIV controls. Lipodystrophy was confirmed and characterized as adipose tissue redistribution in HIVL+ compared with HIVL- and controls, by dual-energy X-ray absorptiometry and by whole body MRI. TNF-alpha secretion from abdominal SAT and circulating levels of IL-6, soluble TNF receptors I and II, and insulin were elevated in HIVL+ relative to HIVL- and/or controls, particularly in HIVL+ undergoing HAART. In the HIV-infected group as a whole, IL-6 secretion from abdominal SAT and serum IL-6 were positively associated with visceral fat and were negatively associated with the relative amount of lower limb adipose tissue (P < 0.01). Decreased leptin and increased lactate secretion from abdominal SAT were specifically associated with HAART. In conclusion, increased cytokine secretion from adipose tissue and increased systemic proinflammatory cytokine activity may play a significant role in the adipose tissue remodeling and/or the metabolic abnormalities associated with the HIV-lipodystrophy syndrome in patients undergoing HAART.
在人类免疫缺陷病毒（HIV）感染期间，高效抗逆转录病毒治疗（HAART）所观察到的脂肪营养不良综合征（脂肪组织重新分布和代谢异常）可能与促炎细胞因子活性增加有关。我们测量了有和没有脂肪营养不良的HIV感染者（分别为HIVL+和HIVL-）以及健康非HIV对照者腹部皮下脂肪组织（SAT）的急性细胞因子（肿瘤坏死因子-α、白细胞介素-6、瘦素）、甘油和乳酸分泌，以及全身细胞因子水平。通过双能X线吸收法和全身磁共振成像，证实了脂肪营养不良，并将其特征描述为与HIVL-和对照相比，HIVL+中的脂肪组织重新分布。相对于HIVL-和/或对照，HIVL+中腹部SAT的肿瘤坏死因子-α分泌以及白细胞介素-6、可溶性肿瘤坏死因子受体I和II以及胰岛素的循环水平升高，特别是在接受HAART的HIVL+中。在整个HIV感染组中，腹部SAT的白细胞介素-6分泌和血清白细胞介素-6与内脏脂肪呈正相关，与下肢脂肪组织的相对量呈负相关（P<0.01）。腹部SAT中瘦素分泌减少和乳酸分泌增加与HAART特异性相关。总之，脂肪组织中细胞因子分泌增加和全身促炎细胞因子活性增加可能在接受HAART的患者中与HIV脂肪营养不良综合征相关的脂肪组织重塑和/或代谢异常中起重要作用。
